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Intracellular decay of N6 -methyladenine (m6A)-containing RNA potentially induces aberrant N6 -methyl-2'-adenine (6mdA) misincorporation into DNA. Biophysically, misincorporated 6mdA may destabilize the DNA duplex in a manner similar to bona fide methylated 6mdA DNA, thereby affecting DNA replication and transcription. Utilizing heavy stable isotope labeling and ultrasensitive UHPLC-MS/MS assay, we demonstrate that intracellular m6A-RNA decay does not generate free 6mdA species, nor lead to any misincorporated DNA 6mdA in most mammalian cell lines tested, unveiling the existence of a sanitation mechanism that prevents 6mdA misincorporation. Depletion of deaminase ADAL increases the levels of free 6mdA species, concomitant with the presence of DNA-misincorporated 6mdA resulting from intracellular RNA m6A decay, suggesting that ADAL catabolizes 6mdAMP in vivo. Furthermore, we show that the overexpression of adenylate kinase 1 (AK1) promotes 6mdA misincorporation, while AK1 knockdown diminishes 6mdA incorporation, in ADAL-deficient cells. We conclude that ADAL together with other factors (such as MTH1) contributes to 2'-deoxynucleotide pool sanitation in most cells but compromised sanitation (e.g., in NIH3T3 cells) and increased AK1 expression may facilitate aberrant 6mdA incorporation. This sanitation mechanism may provide a framework for the maintenance of the epigenetic 6mdA landscape.
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Saneamiento , Espectrometría de Masas en Tándem , Animales , Ratones , Células 3T3 NIH , ADN , Adenilato Quinasa/genética , ARN , MamíferosRESUMEN
Under damp or aquatic conditions, the corrosion products deposited on micro-cracks/pore sites bring about the failure of intrinsically healable organic coatings. Inspired by mussels, a composite coating of poly (methyl methacrylate-co-butyl acylate-co-dopamine acrylamide)/phenylalanine-functionalized boron nitride (PMBD/BN-Phe) is successfully prepared on the reinforcing steel, which exhibits excellent anti-corrosion and underwater self-healing capabilities. The self-healing property of PMBD is derived from the synergistic effect of hydrogen bonding and metal-ligand coordination bonding, and thereby the continuous generation of corrosion products can be significantly suppressed through in situ capture of cations by the catechol group. Furthermore, the corrosion protection ability can be remarkably improved by the labyrinth effect of BN and the inhibition role of Phe, and the desired interfacial compatibility can be formed by the hydrogen bonds between BN-Phe and PMBD matrix. The corrosion current density (icorr) of PMBD/BN-Phe coating is determined as 7.95 × 10-11 A cm-2. The low-frequency impedance modulus (|Z|f = 0.0 1 Hz is remained at 3.47 × 109 Ω cm2, indicating an ultra-high self-healing efficiency (≈89.5%). It is anticipated to provide a unique strategy for development of an underwater self-healing coating and robust durability for application in anti-corrosion engineering of marine buildings.
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AIM: To investigate the associations of metabolic score for insulin resistance (METS-IR) with all-cause and cardiovascular disease (CVD)-specific mortality and the potential mediating role of biological ageing. METHODS: A cohort of 19 204 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 was recruited for this study. Cox regression models, restricted cubic splines, and Kaplan-Meier survival curves were used to determine the relationships of METS-IR with all-cause and CVD-specific mortality. Mediation analyses were performed to explore the possible intermediary role of biological ageing markers, including phenotypic age (PhenoAge) and biological age (BioAge). RESULTS: During a median follow-up of 9.17 years, we observed 2818 deaths, of which 875 were CVD-specific. Multivariable Cox regression showed that the highest METS-IR level (Q4) was associated with increased all-cause (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.14-1.67) and CVD mortality (HR 1.52, 95% CI 1.10-2.12) compared with the Q1 level. Restricted cubic splines showed a nonlinear relationship between METS-IR and all-cause mortality. Only METS-IR above the threshold (41.02 µg/L) was positively correlated with all-cause death. METS-IR had a linear positive relationship with CVD mortality. In mediation analyses, we found that PhenoAge mediated 51.32% (p < 0.001) and 41.77% (p < 0.001) of the association between METS-IR and all-cause and CVD-specific mortality, respectively. For BioAge, the mediating proportions of PhenoAge were 21.33% (p < 0.001) and 15.88% (p < 0.001), respectively. CONCLUSIONS: This study highlights the detrimental effects of insulin resistance, as measured by METS-IR, on all-cause and CVD mortality. Moreover, it underscores the role of biological ageing in mediating these associations, emphasizing the need for interventions targeting both insulin resistance and ageing processes to mitigate mortality risks in metabolic disorders.
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Envejecimiento , Enfermedades Cardiovasculares , Resistencia a la Insulina , Encuestas Nutricionales , Humanos , Enfermedades Cardiovasculares/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Estados Unidos/epidemiología , Adulto , Estudios de Cohortes , Anciano , Síndrome Metabólico/mortalidad , Síndrome Metabólico/epidemiología , Causas de Muerte , Factores de RiesgoRESUMEN
In this paper, a multifunctional device and a design method are proposed based on the vanadium dioxide (VO2)-assisted metamaterial structure. The structure comprises several layers arranged from top to bottom, including a VO2 patch layer, a polyimide (PI) dielectric layer, an elliptical metal layer, a VO2 thin film layer, another PI dielectric layer, and a bottom metal layer. The research results show that the metamaterial structure enables linear-to-linear (LTL) polarization conversion and linear-to-circular (LTC) polarization conversion across multiple frequency bands when the VO2 is in the insulating state. Moreover, as the VO2 material undergoes a transition from the insulating state to the metallic state, the multifunctional structure can function as a broadband absorber, exhibiting an absorption rate of over 90% within the frequency range of 1.751-3.853 THz, with a relative bandwidth of 75%. This versatile conversion device holds great potential for applications in terahertz system and smart system fields.
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BACKGROUND AND AIMS: Exposure to brominated flame retardants (BFRs) has been widely confirmed to impair the normal functioning of the human body system. However, there is a paucity of study on the effects of serum BFRs on bone mineral density (BMD). This study aims to investigate the relationship between exposure to BFRs and BMD in a nationally representative sample of U.S. adults. METHODS: 3079 participants aged between 20 and 80 years with complete data were included in the study. Serum levels of BFRs were measured using automated liquid-liquid extraction and subsequent sample clean-up. The BMD of all participants were assessed by DXA examinations. Generalize linear model, Restricted cubic spline (RCS), subgroup, weighted quantile sum (WQS) and bayesian kernel machine regression (BKMR) were used to estimate the association between serum BFRs and BMD. RESULTS: Multivariate linear regression analyses revealed that, after adjusting for covariates, PBB153 was significantly associated with TF-BMD (ß = 0.0177, 95%CI: 0.0103-0.0252), FN-BMD (ß = 0.009, 95%CI: 0.0036-0.0145), TS-BMD (ß = 0.0081, 95%CI: 0.0013-0.015) and L1-BMD (ß = 0.0144, 95%CI: 0.0075-0.0213). However, the associations lose their statistical significance after further adjustment for sex. BFRs exhibited S-shaped or line-plateau dose-response curves with BMD. In subgroup analyses, BFRs were significantly associated with BMD in participants who were younger than 55 years, female, overweight (BMI >25 kg/m2), and less alcohol consumption. In WQS and BKMR analyses, the effects of BFRs mixtures on BMD differed by sex, and PBDE153, PBDE209 and PBB153 had the highest weights in the WQS regression model. CONCLUSION: This study showed that serum BFRs negatively predicted BMD in men, but not in women or the general population. PBDE153, PBDE209, and PBB153 were significant BMD factors, especially in younger, overweight, and less alcohol consumption individuals.
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Densidad Ósea , Retardadores de Llama , Encuestas Nutricionales , Humanos , Persona de Mediana Edad , Adulto , Retardadores de Llama/análisis , Femenino , Masculino , Densidad Ósea/efectos de los fármacos , Estudios Transversales , Anciano , Estados Unidos , Adulto Joven , Anciano de 80 o más Años , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Ambientales/sangreRESUMEN
Given the markedly different pharmacological activities between enantiomeric isomers, it is crucial to encourage the stereoselective determination of chiral drugs in the biological and pharmaceutical fields, and the combination of drugs makes this analysis more complicated and challenging. Herein, a capillary electrophoresis (CE) method for the enantioseparation of ofloxacin and duloxetine was established, enabling the simultaneous identification of four isomers in nonracemic mixtures with enantiomeric excess (ee%) values exceeding 5%. This was achieved through the integration of theoretical simulation and electron circular dichroism (ECD), all without reliance on individual standards. Molecular modeling explained and verified the migration time differences of these isomers in electrophoretic separation. Moreover, the correlation coefficients (R2 ) between the enantiomeric peak area differentials and ee% were both above 0.99. Recovery rates were quantified using bovine serum as the matrix, with results ranging from 93.32% to 101.03% (RSD = 0.030) and 92.69% to 100.52% (RSD = 0.028) for these two chiral drugs at an ee value of 23.1%, respectively.
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Electroforesis Capilar , Ofloxacino , Clorhidrato de Duloxetina , Ofloxacino/análisis , Estereoisomerismo , Electroforesis Capilar/métodosRESUMEN
The prevalence of cardiovascular diseases continues to be a challenge for global health, necessitating innovative solutions. The potential of high-density lipoprotein (HDL) mimetic nanotherapeutics in the context of cardiovascular disease and the intricate mechanisms underlying the interactions between monocyte-derived cells and HDL mimetic showing their impact on inflammation, cellular lipid metabolism, and the progression of atherosclerotic plaque. Preclinical studies have demonstrated that HDL mimetic nanotherapeutics can regulate monocyte recruitment and macrophage polarization towards an anti-inflammatory phenotype, suggesting their potential to impede the progression of atherosclerosis. The challenges and opportunities associated with the clinical application of HDL mimetic nanotherapeutics, emphasize the need for additional research to gain a better understanding of the precise molecular pathways and long-term effects of these nanotherapeutics on monocytes and macrophages to maximize their therapeutic efficacy. Furthermore, the use of nanotechnology in the treatment of cardiovascular diseases highlights the potential of nanoparticles for targeted treatments. Moreover, the concept of theranostics combines therapy and diagnosis to create a selective platform for the conversion of traditional therapeutic medications into specialized and customized treatments. The multifaceted contributions of HDL to cardiovascular and metabolic health via highlight its potential to improve plaque stability and avert atherosclerosis-related problems. There is a need for further research to maximize the therapeutic efficacy of HDL mimetic nanotherapeutics and to develop targeted treatment approaches to prevent atherosclerosis. This review provides a comprehensive overview of the potential of nanotherapeutics in the treatment of cardiovascular diseases, emphasizing the need for innovative solutions to address the challenges posed by cardiovascular diseases.
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Enfermedades Cardiovasculares , Lipoproteínas HDL , Macrófagos , Monocitos , Humanos , Lipoproteínas HDL/química , Lipoproteínas HDL/metabolismo , Lipoproteínas HDL/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Animales , Enfermedades Cardiovasculares/tratamiento farmacológico , Monocitos/efectos de los fármacos , Nanopartículas/química , Aterosclerosis/tratamiento farmacológico , Placa Aterosclerótica/tratamiento farmacológico , Nanomedicina/métodos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacologíaRESUMEN
OBJECTIVE: This study aimed to reveal the role and mechanism of MG-132 in delaying hyperlipidemia-induced senescence of vascular smooth muscle cells (VSMCs). METHODS: Immunohistochemistry and hematoxylin-eosin staining confirmed the therapeutic effect of MG-132 on arterial senescence in vivo and its possible mechanism. Subsequently, VSMCs were treated with sodium palmitate (PA), an activator (Recilisib) or an inhibitor (Pictilisib) to activate or inhibit PI3K, and CCK-8 and EdU staining, wound healing assays, Transwell cell migration assays, autophagy staining assays, reactive oxygen species assays, senescence-associated ß-galactosidase staining, and Western blotting were performed to determine the molecular mechanism by which MG-132 inhibits VSMC senescence. Validation of the interaction between MG-132 and PI3K using molecular docking. RESULTS: Increased expression of p-PI3K, a key protein of the autophagy regulatory system, and decreased expression of the autophagy-associated proteins Beclin 1 and ULK1 were observed in the aortas of C57BL/6J mice fed a high-fat diet (HFD), and autophagy was inhibited in aortic smooth muscle. MG-132 inhibits atherosclerosis by activating autophagy in VSMCs to counteract PA-induced cell proliferation, migration, oxidative stress, and senescence, thereby inhibiting VSMC senescence in the aorta. This process is achieved through the PI3K/AKT/mTOR signaling pathway. CONCLUSION: MG-132 activates autophagy by inhibiting the PI3K/AKT/mTOR pathway, thereby inhibiting palmitate-induced proliferation, migration, and oxidative stress in vascular smooth muscle cells and suppressing their senescence.
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Autofagia , Senescencia Celular , Leupeptinas , Músculo Liso Vascular , Miocitos del Músculo Liso , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Autofagia/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citología , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Senescencia Celular/efectos de los fármacos , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones , Transducción de Señal/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Leupeptinas/farmacología , Masculino , Ratones Endogámicos C57BL , Ácido Palmítico/farmacología , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Dieta Alta en Grasa/efectos adversosRESUMEN
Jiedu Tongluo (JDTL) Decoction is a traditional Chinese medicine formula containing three herbal ingredients. It is widely used to treat myocardial fibrosis (MF). This study aimed to investigate the molecular mechanism of JDTL Decoction's effect on MF. In this study, 6 compounds of JDTL Decoction were identified by HPLC. HE and Masson staining showed that in the isoproterenol hydrochloride-induced MF rat model, JDTL treatment can protect the myocardial structure and inhibit the expression of collagen III. The immunohistochemistry results also showed that JDTL treatment can significantly reduce vimentin and α-SMA expression, TGF-ß1 expression, and phosphorylation of Smad2/3 in the rat MF model. RCF, a rat cardiac fibroblast cell line, was used as a tool for in vitro study. Using the methods of hydroxyproline detection, MTT, wound healing test, western blot, and double immunofluorescence staining, our in vitro study confirmed the inhibitory effects of JDTL Decoction on proliferation, migration, and trans-difference ability of RCF cells, as well as the molecular mechanisms underlying the inhibitory effects of JDTL Decoction, including the inhibition of TGF-ß1/Smad2/3 pathway through down-regulation of TGF-ß1 expression and phosphorylation of Smad2/3 as well as the inhibition of the expression of vimentin and α-SMA. In conclusion, JDTL Decoction can prolong the process of myocardial fibrosis through the inhibition of the TGFß1/Smad2/3 signaling pathway.
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BACKGROUND: Hexokinase (HK) is the first rate-limiting enzyme of glycolysis, which can convert glucose to glucose-6-phosphate. There are several subtypes of HK, including HK2, which is highly expressed in a variety of different tumors and is closely associated with survival. METHODS: Non-small cell lung cancer (NSCLC) A549 cells with stable overexpression and knockdown of HK2 were obtained by lentivirus transfection. The effects of overexpression and knockdown of HK2 on proliferation, migration, invasion, and glycolytic activity of A549 cells were investigated. The effects on apoptosis were also analyzed using western blot and flow cytometry. In addition, the mitochondria and cytoplasm were separated and the expression of apoptotic proteins was detected by western blot respectively. RESULTS: Upregulation of HK2 could promote glycolysis, cell proliferation, migration, and invasion, which would be inhibited through the knockdown of HK2. HK2 overexpression contributed to cisplatin resistance, whereas HK2 knockdown enhanced cisplatin-induced apoptosis in A549 cells. CONCLUSIONS: Overexpression of HK2 can promote the proliferation, migration, invasion, and drug resistance of A549 cells by enhancing aerobic glycolysis and inhibiting apoptosis. Reducing HK2 expression or inhibiting HK2 activity can inhibit glycolysis and induce apoptosis in A549 cells, which is expected to be a potential treatment method for NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Cisplatino/farmacología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Hexoquinasa/genética , Hexoquinasa/metabolismo , Pulmón/patología , Línea Celular Tumoral , Proliferación Celular , ApoptosisRESUMEN
Although terahertz (THz) spectroscopy demonstrates great application prospects in the fields of fingerprint sensing and detection, traditional sensing schemes face unavoidable limitations in the analysis of trace-amount samples. In this Letter, a novel, to the best of our knowledge, absorption spectroscopy enhancement strategy based on a defect one-dimensional photonic crystal (1D-PC) structure is proposed to achieve strong wideband terahertz wave-matter interactions for trace-amount samples. Based on the Fabry-Pérot resonance effect, the local electric field in a thin-film sample can be boosted by changing the length of the photonic crystal defect cavity, so that the wideband signal of the sample fingerprint can be greatly enhanced. This method exhibits a great absorption enhancement factor, of about 55 times, in a wide terahertz frequency range, facilitating the identification of different samples, such as thin α-lactose films. The investigation reported in this Letter provides a new research idea for enhancing the wide terahertz absorption spectroscopy of trace samples.
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The control of DNA assembly systems on cells has increasingly shown great importance for precisely targeted therapies. Here, we report a controllable DNA self-assembly system based on the regulation of G-quadruplex DNA topology by a reduction-sensitive azobenzene ligand. Specifically, three azobenzene multiamines are developed, and AzoDiTren is identified as the best G4 binder, which displays high affinity and specificity for G4 DNA. Moreover, the reduction-sensitive nature of the azobenzene scaffold allows AzoDiTren to induce a complete change of the G4 topology in a tissue-specific manner, even at high metal cation concentrations. On this basis, the AzoDiTren-induced G4 conformational switch achieves control of the self-assembly of G4-functionalized DNAs on cells. This strategy enables the regulation of G4 and DNA self-assembly by the bioreductant-responsive ligand.
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G-Cuádruplex , Ligandos , ADN , Compuestos Azo/farmacologíaRESUMEN
BACKGROUND: Reports on the proteomic studies of ameloblastoma and other common odontogenic lesions are limited. We thus explored the differential proteins among ameloblastoma, odontogenic keratocyst, dentigerous cyst, and normal gingival tissue using proteomics and identified hub proteins involved in the local aggressiveness and recurrence of ameloblastoma. METHODS: Samples were obtained from 14 patients with ameloblastoma, 6 with odontogenic keratocyst, 9 with a dentigerous cyst, and 5 with normal gingival tissue. Proteins were then extracted, purified, quantified, and analysed using Easy-nLC chromatography and mass spectrometry. Further functional annotation and enrichment analyses were performed using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes on the target protein collection. Protein clustering and protein-protein interaction network analyses were used to screen the hub proteins. Proteins with significant interactions were screened according to their degree index. These results were verified by immunohistochemical staining. Proteins meeting the screening criteria of expression difference ploidy >1.2-fold (upregulation and downregulation) and p < 0.05 were considered differential proteins. RESULTS: In ameloblastoma, 808 differential proteins were upregulated and 505 were downregulated compared with those in odontogenic keratocyst; 309 were upregulated and 453 were downregulated compared with those in dentigerous cyst; and 2210 were upregulated and 829 were downregulated compared with those in normal gingival tissue. The three groups of differential proteins were associated with cellular exosomes, antigen binding, complement activation, human papillomavirus infection, focal adhesion, cell adhesion molecules, and metabolic pathways. CONCLUSION: CDH3 is associated with the local aggressiveness and recurrence of ameloblastoma and is a potential therapeutic target.
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Ameloblastoma , Quiste Dentígero , Quistes Odontogénicos , Tumores Odontogénicos , Humanos , Ameloblastoma/genética , Ameloblastoma/patología , Quiste Dentígero/genética , Quiste Dentígero/patología , Proteómica , Quistes Odontogénicos/genética , Tumores Odontogénicos/genéticaRESUMEN
BACKGROUND AND AIM: Severe acute pancreatitis (SAP) in patients progresses rapidly and can cause multiple organ failures associated with high mortality. We aimed to train a machine learning (ML) model and establish a nomogram that could identify SAP, early in the course of acute pancreatitis (AP). METHODS: In this retrospective study, 631 patients with AP were enrolled in the training cohort. For predicting SAP early, five supervised ML models were employed, such as random forest (RF), K-nearest neighbors (KNN), and naive Bayes (NB), which were evaluated by accuracy (ACC) and the areas under the receiver operating characteristic curve (AUC). The nomogram was established, and the predictive ability was assessed by the calibration curve and AUC. They were externally validated by an independent cohort of 109 patients with AP. RESULTS: In the training cohort, the AUC of RF, KNN, and NB models were 0.969, 0.954, and 0.951, respectively, while the AUC of the Bedside Index for Severity in Acute Pancreatitis (BISAP), Ranson and Glasgow scores were only 0.796, 0.847, and 0.837, respectively. In the validation cohort, the RF model also showed the highest AUC, which was 0.961. The AUC for the nomogram was 0.888 and 0.955 in the training and validation cohort, respectively. CONCLUSIONS: Our findings suggested that the RF model exhibited the best predictive performance, and the nomogram provided a visual scoring model for clinical practice. Our models may serve as practical tools for facilitating personalized treatment options and improving clinical outcomes through pre-treatment stratification of patients with AP.
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Pancreatitis , Humanos , Estudios Retrospectivos , Nomogramas , Índice de Severidad de la Enfermedad , Enfermedad Aguda , Teorema de Bayes , Pronóstico , Aprendizaje AutomáticoRESUMEN
Although terahertz (THz) spectroscopy exhibits a broad application potential in the field of fingerprint sensing and detection, there remain some limitations with the conventional sensing methods for analyzing trace analytes. In this study, a terahertz absorption spectrum boosting method based on the defect one-dimensional (1D) plastic photonic crystal (PPC) structure is proposed to improve the interaction between the terahertz wave and the trace samples. Affected by the Fabry Perot resonance, the local electric field in thin film analytes will be improved. Furthermore, the resonant frequency will be varied by changing the defect width of the 1D PPC. The structure of the uniform planar film sample is easily built and measured. The boosted terahertz absorption spectrum can be obtained by linking the resonant absorption peaks. For the 0.2 µm α-lactose films, a large absorption enhancement factor of about 105 times can be achieved, which has great potential in identifying different analytes. The study performed here gives a novel investigation direction for boosting the broad terahertz absorption spectrum of trace amounts of analytes.
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Research on the interaction between nanoscale materials and light holds significant scientific significance for the development of fields such as optoelectronic conversion and biosensing. The study of micro- and nano-optics has produced numerous outstanding research achievements by utilizing the dielectric optical coupling mechanism and plasmon effects to enhance the interaction between light and matter. These findings have demonstrated tremendous potential for applications in the field of molecular fingerprint sensing. This review focuses on a retrospective analysis of recent research studies in the enhancement of wide-band trace terahertz absorption spectroscopy. The physical mechanisms of using waveguide structures, dielectric metasurfaces/meta-gratings, and spoof surface plasmon polaritons (SSPs) to improve the interaction between light and trace-amount matters are introduced. The new approaches and methods for enhancing broad-band terahertz absorption spectroscopy of trace samples using microstructure designs are discussed. Additionally, we elucidate the scientific ideas and exploratory achievements in enhancing terahertz fingerprint spectroscopy detection. Finally, we provide an outlook on the research and development direction and potential practical applications of absorption spectroscopy enhancement detection.
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Coronary microvascular endothelial cells (CMECs) react to changes in coronary blood flow and myocardial metabolites and regulate coronary blood flow by balancing vasoconstrictors-such as endothelin-1-and the vessel dilators prostaglandin, nitric oxide, and endothelium-dependent hyperpolarizing factor. Coronary microvascular endothelial cell dysfunction is caused by several cardiovascular risk factors and chronic rheumatic diseases that impact CMEC blood flow regulation, resulting in coronary microcirculation dysfunction (CMD). The mechanisms of CMEC dysfunction are not fully understood. However, the following could be important mechanisms: the overexpression and activation of nicotinamide adenine dinucleotide phosphate oxidase (Nox), and mineralocorticoid receptors; the involvement of reactive oxygen species (ROS) caused by a decreased expression of sirtuins (SIRT3/SIRT1); forkhead box O3; and a decreased SKCA/IKCA expression in the endothelium-dependent hyperpolarizing factor electrical signal pathway. In addition, p66Shc is an adapter protein that promotes oxidative stress; although there are no studies on its involvement with cardiac microvessels, it is possible it plays an important role in CMD.
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Isquemia Miocárdica , Enfermedades Vasculares , Humanos , Proteína Transformadora 1 que Contiene Dominios de Homología 2 de Src/metabolismo , Microcirculación , Células Endoteliales/metabolismo , Enfermedades Vasculares/metabolismo , Vasos Coronarios , Endotelio Vascular/metabolismoRESUMEN
Enantioseparation and determination of chiral drugs are of vital importance in biochemical and pharmaceutical research due to the different biological activity, mechanism, and toxicity of individual enantiomers. As a second-generation H(1)-antagonist, cetirizine's pharmaceutical activity is mainly derived from the levocetirizine while the dextro-enantiomer is ineffective and even associated with side effects. Herein, the enantiomers of cetirizine were separated by capillary electrophoresis and identified by electronic circular dichroism. Satisfactory linear relationship was found between the circular dichroism signal at λmax and the electrophoretic peak area difference in the nonracemic mixture of enantiomers. It made possible identification and quantification of cetirizine enantiomers independent of single enantiomer standards. The method's feasibility was demonstrated on the enantiomeric excess experiments of oral drugs measured in human blank urine. Additionally, the separation and determination of cetirizine in human urine after administration were also realized by capillary electrophoresis, indicating the method was sensitive enough for pharmacokinetic study.
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Cetirizina , Electroforesis Capilar , Humanos , Cetirizina/análisis , Cetirizina/farmacocinética , Dicroismo Circular , Estándares de Referencia , Electroforesis Capilar/métodos , EstereoisomerismoRESUMEN
Based on the impedance-matching theory, a double-layer metal structure dynamical focusing cylindrical metalens with a stretchable substrate was designed at the operation frequency of 0.1 THz. The diameter, initial focal length, and NA of the metalens were 80 mm, 40 mm, and 0.7, respectively. The transmission phase of the unit cell structures could cover 0-2π by changing the size of the metal bars, and then the different unit cells were spatially arranged as the designed phase profile for the metalens. When the stretching range of the substrate was about 100%-140%, the focal length changed from 39.3 mm to 85.5 mm, the dynamic focusing range was about 117.6% of the minimum focal length, and the focusing efficiency decreases from 49.2% to 27.9%. Then, by rearranging the unit cell structures, a dynamically adjustable bifocal metalens was numerically realized. Using the same stretching ratio, compared to a single focus metalens, the bifocal metalens can provide a larger focal length control range.
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The terahertz (THz) wave contains abundant spectrum resources and is still in the early stages of development. It has great application potential in biomedical engineering and public security. However, in these areas there are difficulties to overcome like measuring the wide band absorption of a trace mount sample. In this paper, a THz absorption enhancing method is suggested by a multiplexing strategy. By gradually expanding the stretchable substrate of the dielectric metagrating with an oblique THz wave incidence, the resonance peak frequencies can cover the frequency range of 0.48-0.58 THz. Also, the corresponding envelope built by the peaks of the metagrating absorption spectrum with the 0.2 µm α-lactose film can demonstrate 71.55 times boosting compared to the original absorption amplitude of the film. The investigation witnesses possibilities for the detection of biomacromolecular materials.